This application is based on Japanese patent application HEI 11-30342, filed on Feb. 8, 1999, and published as JP-A 2000-229864 on Aug. 22, 2000, the whole contents of which are incorporated herein by reference.
1. Field of the Invention
The present invention relates to a novel antiviral drug containing heteropolyanions of inorganic metal oxides as an active ingredient; and to its use as an antiviral drug.
2. Description of the Related Art
There are a wide variety of viruses that infectiously affect vital bodies for causing various diseases. Against some viruses, highly potent vaccines are developed, but against such viruses as influenza viruses, the vaccines developed for them are low in potency since there exist too many kinds of viruses to be covered by vaccination. Furthermore, in the case of the viruses that cause acute infection for trapping patients into severe conditions, chemotherapies are said to be necessary. The viral infections that are considered to require chemotherapies include infections mainly causing respiratory diseases without any vaccine available (RS virus, influenza virus, etc.), infections that are reactivated and plunge patients into severe conditions under immunosuppressed conditions (herpes simplex virus, cytomegalovirus, etc.), infections that become chronic and keep patients in a carrier state (hepatitis B and C viruses, HIV, etc.), infections of viruses causing vertical infection (rubella virus, varicella-zoster virus, etc.), and infections of hemorrhagic fever viruses such as Ebola hemorrhagic fever. To control these infections respectively, RandD is being conducted on antiviral drugs, but except those having limited effects, no antiviral drug having a broad spectrum of antiviral activity and having little adverse effect has been actually utilized.
Each antiviral drug is developed to target any stage of infection, growth and desorption of the virus concerned. For example, one of inhibitors in the infection stage (adsorption, entering and uncoating of the virus) is dextran sulfate effective against HIV (human immunodeficiency virus), RSV (RS virus), Fluv-A (influenza virus A), etc. Furthermore, inhibitors in the growth stage (replication and transcription of nucleic acid, synthesis and processing of protein and virion formation)include acyclovir effective against HSV (herpes simplex virus), VZV (varicella-zoster virus), etc., AZT (azidothymidine) effective against HIV, ribavirin inhibiting the replication of RNA of various RNA viruses, etc. Inhibitors in the desorption stage (release of virus particles and syncitium formation) include bicyclam effective against HIV and RSV.
However, these conventional antiviral drugs are not always sufficiently high in the antiviral effect or sufficiently low in adverse effects, and also have a problem that resistant strains are likely to be formed. Most of these antiviral drugs are organic compounds. Therefore, for future development of antiviral drugs, it is important to select drugs from a viewpoint different from the conventional one.
An object of this invention is to provide a novel antiviral drug having an spectrum of antiviral activity broader and an antiviral effect stronger than those of the antiviral drugs developed so far such as ribavirin, DS (dextran sulfate) and AZT (azidothymidine) and having a very low adverse effect.
Another object of this invention is to disclose new polyoxometalate anions having a molecular structure quite different from those of inorganic compounds reported to have antiviral effects, i.e., polyoxotungstate salts such as 21-tungsto-9-antimonate (HPA-23), heteropolyanion 5-tungsto-2-antimonate and ammonium 5-tungsto-2-antimonate, and also having both an incomparably strong antiviral effect and low adverse effect.
An aspect of this invention uses an antiviral drug containing alkaline metal salts of heteropolyanions composed of tungstoantimonate (III) (this (III) means trivalent antimony) vanadium-mixed metal oxide ions represented by general formula [(SbW9O33)2V3O3]Pxe2x88x92 (where p is a positive number between 9 to 12). The alkaline ions for forming the salts with the heteropolyanions include alkali metal ions, alkaline earth metal ions, organic or inorganic ammonium ions, and hydride metal (or ammonium) ions. These alkali metal salts may have 50 molecules or less of crystal water. Said antiviral drug mainly composed of the alkaline metal salts is usually provided as a solid or liquid having 0.1 to several mol percent of them dispersed in a matrix, and it is administered into living bodies by any adequate method selected from peroral method, permucosal method, percutaneous method or injection.
It has been demonstrated that the above-mentioned drug as a novel chemical substance is an ideal antiviral drug having a spectrum of antiviral activity broader than those of many known antiviral drugs, and exhibiting a higher potent efficacy and low toxicity. The salt of the heteropolyanion may include cations of various kinds. Of course, when used as a drug, treatment, e.g. of humans, the salt must include pharmaceutically acceptable cations. The compound may be made soluble or insoluble in water as desired depending in part on the cation selected and can be provided as part of various formulations such as tablets and injection drug. Furthermore, the drug is stable also as a preparation. The tungstoantimonate (III) vanadium-mixed metal oxide ions as the main active ingredient of the drug also have an advantage that the molecule can be designed to give the most suitable effect against numerous RNA and DNA viruses, depending on the kind of the alkali ions used for forming the salts and the number of hydrogen ions. With the above effects, the drug exhibits very excellent properties as an antiviral drug.